Optical correction

ABSTRACT

The present disclosure describes compositions which improve visual acuity and to methods for their use.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a continuation application of, claims thebenefit of and claims priority to U.S. patent application Ser. No.12/334,916 filed on Dec. 15, 2008 which claims the benefit of andpriority to British Patent Application No. 0724558.2, filed in theUnited Kingdom on Dec. 15, 2007, the entire disclosures of which areincorporated herein by reference.

BACKGROUND

1. Technical Field

The present invention relates to topical compositions to improve visualacuity and to methods for their use. More particularly, but notexclusively, it relates to eye-drops and the like to ameliorate theeffects of presbyopia, myopia, hypermetropia. astigmatism andcombinations thereof.

2. Background of Related Art

One prevalent form of visual defect is presbyopia, in which the lens ofthe eye becomes relatively rigid, particularly with age, so that itbecomes increasingly difficult to focus. This leads to eyestrain, andultimately to recession of the near point, such that a sufferer ofpresbyopia may be unable to read or work on objects at arm's length.

The conventional response to presbyopia is the use of reading glasses ofappropriate strength to move the wearer's near point sufficiently closeto allow clear vision at convenient reading and working distances.However, since this will probably also move the wearer's far pointcloser, sacrificing their distance vision, reading glasses must usuallybe removed for driving, for example.

Alternatively or additionally, reading glasses are produced whose lensescover only a small portion of the visual field, so that the wearer maylook round them for distance vision. However, the field covered by thelenses may not be sufficient for all purposes.

Bifocal spectacles comprise lenses having zones of different curvatures(or refractive indices), one zone producing a close-in near point forreading, etc, and the other producing a far point at or near infinityfor distance work. Varifocal lenses are similar, but with the zonesgraduating into one another, rather than having a sharp division. Again,the restricted field covered by the “reading” portion of the lens maynot be satisfactory, and many people cannot get used to bifocal lenses.Bifocal lenses are usually more expensive than standard lenses.

Furthermore, many people dislike wearing any form of spectacles forreasons of comfort or for reasons of personal style. Contact lenses havebeen proposed that are akin to bifocal spectacle lenses, but many peopleare uncomfortable with wearing contact lenses.

Surgical interventions include laser surgery to change cornealcurvature, and intraocular implants. Many sufferers from presbyopiawould not be prepared to risk (or pay for) corrective surgery.

There are thus drawbacks with each of the known approaches for improvinga presbyope's ability to see nearby objects.

Myopia is a visual defect in which the cornea is too steeply curved, orthe eyeball is too long, for light from significant distances to befocused on the retina, irrespective of the performance of the lens. Asufferer from myopia thus has a far point closer than infinity,conventionally known as “short sight”. The converse defect is hyperopiaor hypermetropia. in which the cornea is too flat, or the eyeball tooshort, for light from nearby objects to be focused on the retina (again,irrespective of the condition of the eye lens). This leads to a nearpoint a significant distance from the eye, and similar problems to thoseresulting from presbyopia.

Myopia and hypermetropia may be corrected with spectacles or contactlenses of appropriate curvature, or by surgical intervention, akin tothe approaches described above in respect of presbyopia. However, thesame drawbacks are also experienced.

Similar drawbacks are found in existing approaches to correcting variousother minor refractive errors of the eye. A further complication is thatit is not uncommon to suffer from more than one vision defect; forexample, a degree of astigmatism is often present for myopes andhypermetropes.

It is hence an object of the present invention to provide a means forimproving close-in vision for those suffering from presbyopia orhypermetropia. and/or for improving distance vision for those sufferingfrom myopia, that is simple, convenient and comfortable to use and whichobviates the disadvantages of existing approaches. It is also an objectof the present invention to provide a means for ameliorating refractiveerrors of the eye that has the same benefits and/or obviates the samedisadvantages. It is a preferred object of the present invention toprovide a means of addressing multiple vision problems at once. It is afurther object of the present invention to provide a method forameliorating the effects of presbyopia, myopia, hypermetropia and/orrefractive error.

SUMMARY

The present disclosure describes a medicament for topical administrationto a human or animal eye. The medicament includes a first active agentwhich contains a parasympathetic agonist, and a second active agentselected from the group consisting of a sympathetic antagonist, asympathetic agonist and combinations thereof.

In addition, the present disclosure describes methods for improvingvisual acuity and also methods for treating a variety of eye disorders.Some non-limiting examples of the eye disorders include presbyopia,myopia, hypermetropia, astigmatism, and combinations thereof.

In embodiments, a method for improving visual acuity is disclosed whichincludes administering a first active agent containing a parasympatheticagonist to an eye, and then administering a second active agent selectedfrom the group consisting of a sympathetic antagonist, a sympatheticagonist, and combinations thereof.

In embodiments, a method of improving visual acuity includesadministering a single composition comprising a first active agent and asecond active agent to an eye, wherein the first and second activeagents are selected from the group consisting of a parasympatheticagonist, sympathetic antagonist, a sympathetic agonist, and combinationsthereof. In some embodiments, the first active agent contains aparasympathetic agonist.

In other embodiments, a method for treating an eye disorder is disclosedwhich includes administering a first active agent containing aparasympathetic agonist to an eye, and then administering a secondactive agent selected from the group consisting of a sympatheticantagonist, a sympathetic agonist, and combinations thereof.

In still other embodiments, a method for treating an eye disorder isdisclosed which includes administering a single composition comprising afirst active agent and a second active agent to an eye, wherein thefirst and second active agents are selected from the group consisting ofa parasympathetic agonist, sympathetic antagonist, a sympatheticagonist, and combinations thereof. In some embodiments, the first activeagent contains a parasympathetic agonist.

DETAILED DESCRIPTION

According to a first aspect of the present disclosure, there is provideda medicament adapted for topical administration to a human or animaleye, comprising at least two pharmacologically active agents, a firstsaid active agent comprising a parasympathetic agonist, and a secondsaid active agent comprising either a sympathetic antagonist or asympathetic agonist.

In embodiments, the medicament comprises a liquid composition.

Advantageously, the medicament comprises a liquid composition applicableto the eye in drop form.

Alternatively, the medicament may comprise a gel or ointment.

The medicament may comprise a slow release composition, optionallycomprising slow release insert means.

In embodiments, said parasympathetic agonist comprises a substanceadapted to act on acetylcholine receptors.

Advantageously, said parasympathetic agonist comprises pilocarpine.

The medicament may then comprise between 0.05% and 4% pilocarpine,optionally at least 0.25% and optionally no more than approximately0.5%.

Preferably, the second active agent comprises a sympathetic antagonistadapted to act as an α-receptor blocker.

The sympathetic antagonist may advantageously comprise dapiprazole.

The medicament may then comprise between 0.05% and 4% dapiprazole,optionally at least 0.25% and optionally no more than approximately0.5%.

The sympathetic antagonist may comprise thymoxamine.

The medicament may then comprise between 0.05% and 4% thymoxamine,optionally at least 0.25% and optionally no more than approximately0.5%.

The sympathetic antagonist may comprise a β-blocker.

Alternatively, the second active agent may comprise a sympatheticagonist.

The sympathetic agonist may comprise brimonidine.

The medicament may then comprise between 0.01% and 4% brimonidine. andoptionally at least about 0.1% thereof.

The sympathetic agonist may comprise iopidine.

The medicament may comprise at least one further component adapted toreduce discomfort of an eye treated with the medicament.

According to a second aspect of the present invention, there is provideda use of a combination of a first pharmacologically active agentcomprising a parasympathetic agonist and a second pharmacologicallyactive agent comprising a sympathetic antagonist or a sympatheticagonist in the manufacture of a medicament adapted for topicalapplication to a human or animal eye in order to improve visual acuity.

Said medicament may be adapted to treat presbyopia.

Said medicament may be adapted to treat myopia.

Said medicament may be adapted to treat hypermetropia.

Said medicament may be adapted to improve night or low-light vision.

Said medicament may be adapted to treat defects of visual acuity such asastigmatism.

Said medicament may be adapted to treat more than one of the aboveconditions simultaneously.

According to a third aspect of the present invention, there is provideda method for improving visual acuity comprising the step ofadministering to an eye a combination of a first pharmacologicallyactive agent comprising a parasympathetic agonist and a secondpharmacologically active agent comprising a sympathetic antagonist or asympathetic agonist.

Preferably, the method comprises the steps of providing a singlecomposition comprising each of said first and second active agents, andadministering said composition to the eye.

Alternatively, the method comprises the steps of administeringsequentially to the eye respective compositions containing said firstand second active agents.

Embodiments of the present invention will now be more particularlydescribed by way of example.

An otherwise conventional eye-drop formulation was prepared, into whichwas incorporated 0.5% by weight dapiprazole and 0.5% by weightpilocarpine, to produce a first eye-drop formulation embodying thepresent invention. Dapiprazole is classified as a sympatheticantagonist; pilocarpine as a parasympathetic agonist.

In a first example, a patient aged sixty-three presented as an emmetrope(not requiring glasses for functional distance vision). The patient'svision was tested, the first eye-drop formulation was administered, andthe patient's vision was then re-tested. Within twenty months ofadministration, the patient's unaided distance vision in each eye hadimproved by a line on the Snellen chart, from 6/6 to 6/5. The refractiondid not change. The patient's unaided reading vision improved from N12to N4.5 at a reading distance of one third of a meter. The patient'snight vision improved qualitatively, as the patient noted less haloesand glare, and quantitatively, from 6/6 to 6/5 in dim conditions. Theseeffects were maintained for two hours and some for at least four hours.

The first eye-drop formulation thus improves both near and distancevision. In a second example, a patient aged fifty presented as a −4Dioptre myope (requiring glasses for functional distance vision). Again,the patient's vision was tested before and after the first eye-dropformulation was administered. Within half an hour of administration, thepatient's unaided distance vision improved from being able to countfingers (but not to read the Snellen chart) to 6/36 on the chart.Wearing distance-corrected glasses, the patient's reading vision at adistance of one third of a meter improved from N12 to N4.5. Therefraction did not change. Quality of night vision improved as thepatient noted less haloes and glare, and night vision also improvedquantitatively from 6/6 to 6/5 in dim conditions. The effects again weremaintained for two hours and some for at least four hours.

In a third example, a patient aged forty-nine presented as a +4 Dioptrehypermetrope (longsighted and requiring glasses for useful readingvision). The patient's vision was tested before and after administrationof the first eye-drop formulation. Within half an hour ofadministration, the patient's unaided distance vision improved on theSnellen chart from 6/60 to 6/24. The patient's unaided reading vision atone third of a meter improved from N18 to N4.5. The refraction did notchange. Quality of night vision improved, the patient noting less haloesand glare, and night vision also improved quantitatively from 6/6 to 6/5in dim conditions. The effects were maintained for two hours and somefor at least four hours.

In all three examples, no significant discomfort was reported.

A second eye-drop formulation embodying the present invention wasprepared by incorporating 0.1% by weight brimonidine and 0.25% by weightpilocarpine into an otherwise conventional eye-drop formulation.Brimonidine is classified as a sympathetic agonist: pilocarpine, asnoted above, is considered to be a parasympathetic agonist.

The second eye-drop formulation was tested on the three patientsreferred to above. In each case, administration of the second eye-dropformulation produced almost identical effects to the first eye-dropformulation, above.

A third and fourth eye-drop formulation were made up, containing 0.5%dapiprazole and 0.5% pilocarpine, respectively. Administration of thethird and fourth eye-drop formulations immediately sequentially to apatient's eyes produced results substantially identical to those fromthe first eye-drop formulation (which contained the same activecomponents, pre-mixed). Thus, the eye-drop formulations of the presentinvention may in effect be produced in situ in the patient's eye, shouldthis be convenient. (NB: the effects of the third or fourth eye-dropformulations administered alone would be substantially inferior to thoseof the first formulation, or to those of the third and fourthformulations, either mixed before administration or in the eye).

There are signs that the eye-drop formulations of the present inventionalso obviate the effects of astigmatism. Thus, they will be useful forthe many patients who suffer from combinations of vision problems, suchas myopia coupled with astigmatism. (Such effects make prescribing andproducing appropriate spectacle lenses, or other conventionalapproaches, particularly difficult).

It is particularly notable from the above results that not only do thecompositions of the present invention significantly improve the unaideddistance vision of myopes and the unaided close-up vision ofhypermetropes, but they also improve the clarity of close-up vision formyopes, distance vision for hypermetropes and vision both near and farfor emmetropes. It is also evident from these results that presbyopeswould also benefit from treatment with these compositions. Presbyopiausually takes the form of difficulty in focussing on nearby objects(accommodation). Compositions such as those of the present invention,which do not act by changing refraction, are thus likely to be moredesirable and effective than those compositions that have occasionallybeen proposed in the past, which do change refraction. The effect onnight vision haloes, etc, suggests that other form of refractive errormight also be ameliorated.

The eye-drops of the present invention may thus be used temporarily toalleviate the effects of conditions such as myopia and hypermetropia orto improve adequate vision further. It is envisaged that, due to thelack of side-effects and drawbacks discovered in testing to date, theseeye-drops might well be suitable for self-selection andself-administration, rather than needing to be prescribed by a qualifiedmedical practitioner.

Thus, the eye-drops of the present invention could be used in place ofcorrective glasses or contact lenses, either as a general practice: forvariety; or in particular circumstances where glasses and/or contactlenses might not be practical or convenient (e.g. contact sports).

The exact physiological mode of action of these combinations ofpharmaceuticals has not yet been established. The most significant andunexpected feature of their action appears to be that combiningparasympathetic agonists and sympathetic antagonists, agents havinglargely opposite modes of action, produces beneficial synergies relativeto either agent used separately, while their possible adverse effectsappear largely to cancel out.

It is also most unexpected that parasympathetic agonists and sympatheticagonists appear to co-operate synergistically, without significantside-effects.

It is believed that at least part of the benefit of the combinationsdescribed is because they seem to have little or no net effect on theciliary muscles of the eye, which act to alter the shape and hencerefraction of the lens.

While the examples above describe application in the form of eye-drops,other forms of topical application to the eye may be possible. There isno reason to believe that spraying compositions with the samecombinations of active agents into the eye; applying a gel or ointmentto the eye; or even using an ocular insert containing a slow-releasepreparation of one of the above combination of active agents would notwork similarly well.

It is possible that certain otherwise suitable active agents might leadto issues with general discomfort in the eye, or even specificside-effects such as red-eye, in which blood vessels of the scleradilate so far that some or all of the white of the eye appears red. Thetreatment could be completed with separate administration of furthercompositions selected on a symptomatic basis. However, it is probablymore convenient to incorporate the appropriate treatment agents into thecompositions of the present invention, particularly where theside-effect is frequently encountered.

As well as the active agents exemplified above, others that are believedto be particularly suitable for the compositions of the presentinvention include: thymoxamine, a sympathetic antagonist (substitutablefor dapiprazole); and iopidine, a sympathetic agonist (substitutable forbrimonidine). The class of drugs generally referred to as beta-blockersmay be considered as sympathetic antagonists, and hence some or all ofthat class may well be usable in place of dapiprazole, above.

It is also believed that an opiate could be substituted for either theparasympathetic agonist or the sympathetic antagonist/agonist in thecompositions above. Indeed, a composition containing an opiate as itssole or main active component is predicted to be effective in thetreatment of the conditions listed above.

What is claimed is:
 1. A method for treating an astigmatism andpresbyopia: administering a first active agent comprising about 0.05% toabout 4% pilocarpine to an eye suffering from the astigmatism andpresbyopia, and administering a second active agent comprising about0.05% to about 4% thymoxamine.
 2. A method for treating an astigmatismand presbyopia comprising: administering a single composition to an eyesuffering from the astigmatism and presbyopia, the single compositioncomprising a first active agent comprising about 0.05% to about 4%pilocarpine and a second active agent comprising about 0.05% to about 4%thymoxamine.
 3. The method of claim 2 wherein administering the singlecomposition to the eye suffering from an astigmatism and presbyopia doesnot change refraction of a lens of the eye.
 4. The method of claim 1wherein administering the first active agent and administering thesecond active agent to the eye suffering from an astigmatism andpresbyopia does not change refraction of a lens of the eye.
 5. Themethod of claim 1 wherein the first active agent is in a form of an eyedrop, and the second active agent is in a form of an eye drop.
 6. Themethod of claim 2 wherein the single composition is in a form of an eyedrop.
 7. A method for treating an astigmatism and myopia comprising:administering a first active agent comprising about 0.05% to about 4%pilocarpine to an eye suffering from the astigmatism and myopia, andadministering a second active agent comprising about 0.05% to about 4%thymoxamine.
 8. The method of claim 7 wherein administering the firstactive agent and administering the second active agent to the eyesuffering from an astigmatism and myopia does not change refraction of alens of the eye.
 9. The method of claim 7 wherein the first active agentis in a form of an eye drop, and the second active agent is in a form ofan eye drop.
 10. A method for treating an astigmatism and myopiacomprising: administering a single composition to an eye suffering fromthe astigmatism and myopia, the single composition comprising a firstactive agent comprising about 0.05% to about 4% pilocarpine and a secondactive agent comprising about 0.05% to about 4% thymoxamine.
 11. Themethod of claim 10 wherein administering the single composition to theeye suffering from an astigmatism and myopia does not change refractionof a lens of the eye.
 12. The method of claim 10 wherein the singlecomposition is in a form of an eye drop.